The effects of presynaptic calcium channel modulation by roscovitine on transmitter release at the adult frog neuromuscular junction

Soyoun Cho, Stephen D. Meriney

    Research output: Contribution to journalArticlepeer-review

    30 Scopus citations

    Abstract

    Calcium (Ca2+) influx through presynaptic calcium channels triggers transmitter release, and any alterations in the gating of these calcium channels results in changes in the magnitude of transmitter released. We used (R)-roscovitine, a cyclin-dependent kinase inhibitor that also appears to act directly on calcium channels, as a tool to modulate presynaptic calcium influx and study effects on transmitter release. We show that this compound increased the quantal content of acetylcholine released from the Rana frog motor nerve terminal (by 149%) without changing paired-pulse facilitation (under low calcium conditions). In contrast, exposure to 3,4-diaminopyridine (DAP; which similarly affects transmitter release by partially blocking potassium channels, altering the shape of the presynaptic action potential, and indirectly increasing calcium entry) increased paired-pulse facilitation (by 23%). In addition, we show that (R)-roscovitine predominately slowed deactivation kinetics of calcium current (by 427%) recorded from Xenopus frog motoneurons, and as a result, increased the integral of calcium channel current evoked by a physiological action potential waveform (by 44%). Because we did not observe any significant effects of structurally related cyclin-dependent kinase inhibitors [(S)-roscovitine or olomoucine] on evoked transmitter release or calcium current kinetics, it appears that these effects of (R)-roscovitine are independent of cyclin-dependent kinases (cdks). In summary, we hypothesize that (R)-roscovitine effects on transmitter release at the adult frog neuromuscular junction (NMJ) are mediated by its effects on calcium channel gating, and these effects increase our understanding of calcium triggered secretion at this synapse.

    Original languageEnglish (US)
    Pages (from-to)3200-3208
    Number of pages9
    JournalEuropean Journal of Neuroscience
    Volume23
    Issue number12
    DOIs
    StatePublished - Jun 2006

    Keywords

    • Calcium
    • Motoneuron
    • Paired-pulse facilitation Rana pipiens
    • Xenopus laevis

    ASJC Scopus subject areas

    • Neuroscience(all)

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